tbuckley/cabot-search huggingface dataset:
Comprehensive Diagnosis and Management of POEMS Syndrome
Authors: Shirley D’Sa, Jahanzaib Khwaja, Stephen Keddie, Ryan YS Keh, Duncan Smyth, Ruth Ronneberger, Suraiya Dubash, Suganya Sivabalasingham, Simon Wan, Chandrashekar Hoskote, Stephanie Baldeweg, Jonathan Sive, Michael P. Lunn
Journal: HemaSphere (2022)

Polyneuropathy Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes syndrome is a rare multisystem condition with a range of manifestations which are often overlooked as trivial comorbidities, until their whole triggers the possibility of the diagnosis. The diagnosis is typically delayed by 12–16 months, by which time patients can be severely disabled. There are no established consensus guidelines. We provide clinicians a comprehensive blueprint for managing POEMS from diagnostic suspicion through the work-up, selection of therapy, follow-up, and treatment of relapse based on published evidence and our large single-center experience. A multidisciplinary approach is essential including expert hematologists, neurologists, histopathologists, radiologists, and neurophysiologists. The aim of treatment is to eradicate the underlying plasma cell dyscrasia, but there are limited trial data to guide treatment decisions. Supportive care considerations include management of endocrinopathy, neuropathy, thrombosis, and infection. Response assessment is centered on clinical, neuropathy, hematological, vascular endothelial growth factor, and radiological criteria. Future clinical trials are welcomed in this setting where evidence is limited.
Spectral Analysis of Heart Rate Variability in Time-Varying Conditions and in the Presence of Confounding Factors
Authors: Leif Sörnmo, Raquel Bailón, Pablo Laguna
Journal: IEEE Reviews in Biomedical Engineering (2022)

The tools for spectrally analyzing heart rate variability (HRV) has in recent years grown considerably, with emphasis on the handling of time-varying conditions and confounding factors. Time-frequency analysis holds since long an important position in HRV analysis, however, this technique cannot alone handle a mean heart rate or a respiratory frequency which vary over time. Overlapping frequency bands represents another critical condition which needs to be dealt with to produce accurate spectral measurements. The present survey offers a comprehensive account of techniques designed to handle such conditions and factors by providing a brief description of the main principles of the different methods. Several methods derive from a mathematical/statistical model, suggesting that the model can be used to simulate data used for performance evaluation. The inclusion of a respiratory signal, whether measured or derived, is another feature of many recent methods, e.g., used to guide the decomposition of the HRV signal so that signals related as well as unrelated to respiration can be analyzed. It is concluded that the development of new approaches to handling time-varying scenarios are warranted, as is benchmarking of performance evaluated in technical as well as in physiological/clinical terms.
Development of monoclonal antibody-based antigens detection assays for orthopoxvirus and monkeypox virus
Authors: Mengjun Li, Yuelin Wang, Chaohui Li, Rui Xu, Jiayin Chen, Junfang Zhang, Minghui Yang, Yushan Jiang, Yuqing Li, Zhujun Zeng, Zhiguang Wu, Wei Zhao, Bo Wu, Chenguang Shen
Journal: Journal of Infection (2022)
A State of Natriuretic Peptide Deficiency
Authors: Michael Nyberg, Dijana Terzic, Trine P Ludvigsen, Peter D Mark, Natasha B Michaelsen, Steen Z Abildstrøm, Mads Engelmann, A Mark Richards, Jens P Goetze
Journal: Endocrine Reviews (2022)

Measurement of natriuretic peptides (NPs) has proven its clinical value as biomarker, especially in the context of heart failure (HF). In contrast, a state of partial NP deficiency appears integral to several conditions in which lower NP concentrations in plasma presage overt cardiometabolic disease. Here, obesity and type 2 diabetes have attracted considerable attention. Other factors-including age, sex, race, genetics, and diurnal regulation-affect the NP "armory" and may leave some individuals more prone to development of cardiovascular disease. The molecular maturation of NPs has also proven complex, with highly variable O-glycosylation within the biosynthetic precursors. The relevance of this regulatory step in post-translational propeptide maturation has recently become recognized in biomarker measurement/interpretation and cardiovascular pathophysiology. An important proportion of people appear to have reduced effective net NP bioactivity in terms of receptor activation and physiological effects. The state of NP deficiency both entails a potential for further biomarker development and could also offer novel pharmacological possibilities. Alleviating the state of NP deficiency before development of overt cardiometabolic disease in selected patients could be a future path for improving precision medicine.
Metal-organic frameworks: A promising option for the diagnosis and treatment of Alzheimer's disease
Authors: Shima Tajahmadi, Hossein Molavi, Farhad Ahmadijokani, Amir Shamloo, Akbar Shojaei, Mohammad Sharifzadeh, Mashallah Rezakazemi, Ali Fatehizadeh, Tejraj M. Aminabhavi, Mohammad Arjmand
Journal: Journal of Controlled Release (2022)
Elevated neutrophil extracellular traps by HBV‐mediated S100A9‐TLR4/RAGE‐ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma
Authors: Xi Zhan, Rui Wu, Xue‐Hua Kong, Yan You, Kun He, Xiao‐Yu Sun, Yong Huang, Wei‐Xian Chen, Liang Duan
Journal: Cancer Communications (2022)

Neutrophil extracellular traps (NETs) are considered significant contributors to cancer progression, especially metastasis. However, it is still unclear whether NETs are involved in hepatitis B virus (HBV)-related hepatocarcinogenesis and have potential clinical significance during evaluation and management for hepatocellular carcinoma (HCC). In this study, we aimed to investigate the functional mechanism of NETs in HBV-related hepatocarcinogenesis and their clinical significance. A total of 175 HCC patients with and without HBV infection and 58 healthy controls were enrolled in this study. NETs were measured in tissue specimens, freshly isolated neutrophils and blood serum from these patients, and the correlation of circulating serum NETs levels with malignancy was evaluated. The mechanism by which HBV modulates NETs formation was explored using cell-based studies. In addition, in vitro and in vivo experiments were further performed to clarify the functional mechanism of NETs on the growth and metastasis of HCC. We observed an elevated level of NETs in blood serum and tissue specimens from HCC patients, especially those infected with HBV. NETs facilitated the growth and metastasis of HCC both in vitro and in vivo, which were mainly dominated by increased angiogenesis, epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinases (MMPs)-induced extracellular matrix (ECM) degradation and NETs-mediated cell trapping. Inhibition of NETs generation by DNase 1 effectively abrogated the NETs-aroused HCC growth and metastasis. In addition, HBV-induced S100A9 accelerated the generation of NETs, which was mediated by activation of toll-like receptor (TLR4)/receptor for advanced glycation end products (RAGE)-reactive oxygen species (ROS) signaling. Further, circulatory NETs were found to correlate with viral load, TNM stage and metastasis status in HBV-related HCC, and the identified NETs could predict extrahepatic metastasis, with an area under the ROC curve (AUC) of 0.83 and 90.3% sensitivity and 62.8% specificity at a cutoff value of 0.32. Our findings indicated that activation of RAGE/TLR4-ROS signaling by HBV-induced S100A9 resulted in abundant NETs formation, which subsequently facilitated the growth and metastasis of HCC cells. More importantly, the identified circulatory NETs exhibited potential as an alternative biomarker for predicting extrahepatic metastasis in HBV-related HCC.
Efficacy of High-Flow Nasal Cannula Oxygen Therapy in Reducing Future Exacerbations for Patients with Stable Hypercapnia with Chronic Obstructive Pulmonary Disease
Authors: Zhenfeng He, Lili Guan, Shanshan Zha, Jianyi Niu, Luqian Zhou, Wei Fu, Shengchuan Feng, Rongchang Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
Disparity in checkpoint inhibitor utilization among commercially insured adult patients with metastatic lung cancer
Authors: Meng Li, Kaiping Liao, Alice J Chen, Tina Cascone, Yu Shen, Qian Lu, Ya-Chen Tina Shih
Journal: JNCI Journal of the National Cancer Institute (2022)

There is a lack of evidence from nationwide samples on the disparity of initiating immune checkpoint inhibitors (ICIs) after metastatic lung cancer diagnosis.We identified metastatic lung cancer patients diagnosed between 2015 and 2020 from a large, nationwide commercial claims database. We analyzed the time from metastatic lung cancer diagnosis to ICI therapy using Cox proportional hazard models. Independent variables included county-level measures (quintiles of percentage of racialized population, quintiles of percentage of population below poverty, urbanity, and density of medical oncologists) and patient characteristics (age, sex, Charlson comorbidity index, Medicare Advantage, and year of diagnosis). All tests were 2-sided.A total of 17 022 patients were included. Counties with a larger proportion of racialized population appeared to be more urban, have a greater percentage of its residents in poverty, and have a higher density of medical oncologists. In Cox analysis, the adjusted hazard ratio of the second, third, fourth, and highest quintile of percentage of racialized population were 0.89 (95% confidence interval [CI] = 0.82 to 0.98), 0.85 (95% CI = 0.78 to 0.93), 0.78 (95% CI = 0.71 to 0.86), and 0.71 (95% CI = 0.62 to 0.81), respectively, compared with counties in the lowest quintile. The slower ICI therapy initiation was driven by counties with the highest percentage of Hispanic population and other non-Black racialized groups.Commercially insured patients with metastatic lung cancer who lived in counties with greater percentage of racialized population had slower initiation of ICI therapy after lung cancer diagnosis, despite greater density of oncologists in their neighborhood.
A Review in On-Body Compression Using Soft Actuators and Sensors: Applications, Mechanisms, and Challenges
Authors: Alireza Golgouneh, Lucy E. Dunne
Journal: IEEE Reviews in Biomedical Engineering (2022)

Body compression through a garment or inflatable pneumatic mechanism has various applications in aesthetic, athletic, robotics, haptics, astronautics, and especially medical fields for treatment of various disorders such as varicose veins, lymphedema, deep vein thrombosis, and orthostatic intolerance. Traditionally, compression has been done through under-sized (e.g. elastic) or size-adjustable (e.g. inflatable) compression garments. Such systems are designed to apply substantially uniform pressure on the body. However, due to reasons such as anatomical variations and body posture change, different levels of compression may be applied to the body. Further, a high level of discomfort and non-compliance is reported among patients due to donning difficulties. Therefore, there have been some efforts to make compression garments smart by employing advanced functional soft materials and actuators (such as Shape Memory Alloy (SMA), Shape Memory Polymer (SMP), Electroactive polymer (EAP), etc.) as well as soft force-pressure sensors so that the compression level could be controlled and regulated for each person or specific tasks. However, despite these advances, there are still challenges to accurately controlling the on-body compression level that are mainly due to the inherent characteristics of the soft actuators or sensors and the sophisticated human body conditions. In this paper, we will first investigate the soft actuators and sensors that have the potential to be used for on-body compression applications. Then, integrated soft sensing-actuation systems for interfacial compression purposes are studied. Finally, the challenges that might be associated with this work are introduced.
American College of Rheumatology Guidance for <scp>COVID</scp>‐19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 5
Authors: Jeffrey R. Curtis, Sindhu R. Johnson, Donald D. Anthony, Reuben J. Arasaratnam, Lindsey R. Baden, Anne R. Bass, Cassandra Calabrese, Ellen M. Gravallese, Rafael Harpaz, Andrew Kroger, Rebecca E. Sadun, Amy S. Turner, Eleanor Anderson Williams, Ted R. Mikuls
Journal: Arthritis & Rheumatology (2022)

To provide guidance to rheumatology providers on the use of COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases (RMDs).A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious diseases specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings.Despite a paucity of direct evidence, statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines, including supplemental/booster dosing, in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination.These guidance statements are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.
Distinct Genetically Determined Origins of <i>Myd88</i>/<i>BCL2</i>-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies
Authors: Ruth Flümann, Julia Hansen, Benedikt W. Pelzer, Pascal Nieper, Tim Lohmann, Ilmars Kisis, Tobias Riet, Viktoria Kohlhas, Phuong-Hien Nguyen, Martin Peifer, Nima Abedpour, Graziella Bosco, Roman K. Thomas, Moritz Kochanek, Jacqueline Knüfer, Lorenz Jonigkeit, Filippo Beleggia, Alessandra Holzem, Reinhard Büttner, Philipp Lohneis, Jörn Meinel, Monika Ortmann, Thorsten Persigehl, Michael Hallek, Dinis Pedro Calado, Markus Chmielewski, Sebastian Klein, Joachim R. Göthert, Bjoern Chapuy, Branko Zevnik, F. Thomas Wunderlich, Bastian von Tresckow, Ron D. Jachimowicz, Ari M. Melnick, Hans Christian Reinhardt, Gero Knittel
Journal: Blood Cancer Discovery (2022)

Genomic profiling revealed the identity of at least 5 subtypes of diffuse large B-cell lymphoma (DLBCL), including the MCD/C5 cluster characterized by aberrations in MYD88, BCL2, PRDM1, and/or SPIB. We generated mouse models harboring B cell-specific Prdm1 or Spib aberrations on the background of oncogenic Myd88 and Bcl2 lesions. We deployed whole-exome sequencing, transcriptome, flow-cytometry, and mass cytometry analyses to demonstrate that Prdm1- or Spib-altered lymphomas display molecular features consistent with prememory B cells and light-zone B cells, whereas lymphomas lacking these alterations were enriched for late light-zone and plasmablast-associated gene sets. Consistent with the phenotypic evidence for increased B cell receptor signaling activity in Prdm1-altered lymphomas, we demonstrate that combined BTK/BCL2 inhibition displays therapeutic activity in mice and in five of six relapsed/refractory DLBCL patients. Moreover, Prdm1-altered lymphomas were immunogenic upon transplantation into immuno-competent hosts, displayed an actionable PD-L1 surface expression, and were sensitive to antimurine-CD19-CAR-T cell therapy, in vivo.
Hypomagnesemia and Cardiovascular Risk in Type 2 Diabetes
Authors: Lynette J Oost, Cees J Tack, Jeroen H F de Baaij
Journal: Endocrine Reviews (2022)

Abstract Hypomagnesemia is 10-fold more common in individuals with type 2 diabetes (T2D) than in the healthy population. Factors that are involved in this high prevalence are low Mg2+ intake, gut microbiome composition, medication use, and presumably genetics. Hypomagnesemia is associated with insulin resistance, which subsequently increases the risk to develop T2D or deteriorates glycemic control in existing diabetes. Mg2+ supplementation decreases T2D-associated features like dyslipidemia and inflammation, which are important risk factors for cardiovascular disease (CVD). Epidemiological studies have shown an inverse association between serum Mg2+ and the risk of developing heart failure (HF), atrial fibrillation (AF), and microvascular disease in T2D. The potential protective effect of Mg2+ on HF and AF may be explained by reduced oxidative stress, fibrosis, and electrical remodeling in the heart. In microvascular disease, Mg2+ reduces the detrimental effects of hyperglycemia and improves endothelial dysfunction; however, clinical studies assessing the effect of long-term Mg2+ supplementation on CVD incidents are lacking, and gaps remain on how Mg2+ may reduce CVD risk in T2D. Despite the high prevalence of hypomagnesemia in people with T2D, routine screening of Mg2+ deficiency to provide Mg2+ supplementation when needed is not implemented in clinical care as sufficient clinical evidence is lacking. In conclusion, hypomagnesemia is common in people with T2D and is involved both as cause, probably through molecular mechanisms leading to insulin resistance, and as consequence and is prospectively associated with development of HF, AF, and microvascular complications. Whether long-term supplementation of Mg2+ is beneficial, however, remains to be determined.
Temporal Trends in the Incidence of Hemophagocytic Lymphohistiocytosis: A Nationwide Cohort Study From England 2003–2018
Authors: Joe West, Peter Stilwell, Hanhua Liu, Lu Ban, Mary Bythell, Tim R. Card, Peter Lanyon, Vasanta Nanduri, Judith Rankin, Mark J. Bishton, Colin J. Crooks
Journal: HemaSphere (2022)

Hemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality, and is increasingly being diagnosed. We aimed to quantify the incidence of diagnosed HLH and examine temporal trends in relation to age and associated diseases. Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between January 1, 2003, and December 31, 2018. We calculated incidence rates of diagnosed HLH per million population by calendar year, age group, sex, and associated comorbidity (hematological malignancy, inflammatory rheumatological or bowel diseases [IBD]). We modeled trends in incidence and the interactions between calendar year, age, and associated comorbidity using Poisson regression. There were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (incidence rate ratio [IRR] 2018 compared to 2003: 3.88, 95% confidence interval [CI] 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11, 95% CI 1.09 to 1.12). There was a transition across age groups with greater increases in those aged 5–14 years of HLH associated with rheumatological disease/IBD compared with hematological malignancy, with similar increases in HLH associated with both comorbidities for those 15–54, and greater increases in HLH associated with hematological malignancies for those 55 years and older. The incidence of HLH in England has quadrupled between 2003 and 2018. Substantial variation in the incidence occurred with inflammatory rheumatological diseases/IBD-associated HLH increasing more among the younger age groups, whereas in older age groups, the largest increase was seen with hematological malignancy-associated HLH.
Sarah Hallett and Mike Kemp: Doctors are “thwarted” by politicians’ mismanagement of the NHS, say junior leaders
Authors: Elisabeth Mahase
Journal: BMJ (2022)

With 12 years’ combined experience of representing their colleagues at a national level, the former BMA Junior Doctors Committee co-chairs <b>Sarah Hallett</b> and <b>Mike Kemp</b> talk to <i>The BMJ</i> about pay erosion, flexibility in training, and giving the government an ultimatum
Spatiotemporal Control of Vascular Ca <sub>V</sub> 1.2 by α1 <sub>C</sub> S1928 Phosphorylation
Authors: Miguel Martín-Aragón Baudel, Victor A. Flores-Tamez, Junyoung Hong, Gopyreddy R. Reddy, Pauline Maillard, Abby E. Burns, Kwun Nok Mimi Man, Kent C. Sasse, Sean M. Ward, William A. Catterall, Donald M. Bers, Johannes W. Hell, Madeline Nieves-Cintrón, Manuel F. Navedo
Journal: Circulation Research (2022)

L-type Ca
Anchoring endoscopic mucosal resection for colorectal polyps – keep this weapon in mind
Authors: Gregorios A. Paspatis
Journal: Endoscopy (2022)

It has been a long time since conventional endoscopic mucosal resection (C-EMR) was launched as a procedure of choice for the treatment of nonpedunculated colorectal polyps; however, for lesions of > 20 mm, piecemeal EMR has been associated with significant incomplete resection rates. The sequence from incomplete resection to colon cancer is well documented in the literature. Therefore, techniques that increase the rate of en bloc R0 resection with EMR are of the utmost importance. To this end, modified EMR techniques such as precutting EMR or anchoring EMR (A-EMR) have been proposed. A-EMR was first described in the last decade [1] [2], but what is this technique and what is its merit? A small incision is created with the tip of the snare in the submucosa of the mucosal area surrounding the polyp. Subsequently, the snare tip is anchored in the defect, with the aim of both preventing slippage of the snare and widening the diameter of the open snare.
Dysfunction of norepinephrine and its metabolites in Alzheimer's dementia – A review with meta-analysis
Authors: Isabel Portela Moreira, Teresa Henriques, Maria Augusta Vieira-Coelho, Joana Guimarães
Journal: Ageing Research Reviews (2022)

Some studies point locus coeruleus cell loss, the central nervous system main source of norepinephrine, to be one of the earliest neuropathological events of Alzheimer's disease (AD). However, there are conflicting reports regarding the level of norepinephrine and its metabolites (3-Methoxy-4-hydroxyphenylglycol (MHPG), 3,5-dihydroxyphenylglycine (DHPG) and 3,4 -dihydroxyphenylglycolaldehyde (DOPEGAL)) in AD patients. Uncover these alterations may be a key factor for understanding cognitive deficits and AD pathology. We review the literature that compare norepinephrine and its metabolites between AD patients and non-demented controls. A meta-analysis did not reveal significant statistical differences, but there was a trend towards a lower level of norepinephrine of AD, with almost no difference in MHPG in the cerebrospinal fluid. Regarding MHPG in plasma, DHPG and DOPEGAL we only performed a qualitative analyse due to the small or absent number of studies. These findings point to a decrease in norepinephrine, what is in line with locus coeluleus cell loss in AD. The absence of statistical difference and an equal level of MHGP could indicate a compensatory mechanism.